sign in sign up
<<
Home , Acute myeloid leukemia, Azacitidine, Cladribine, Cytarabine, Daunorubicin, Decitabine

Acute Myeloid (AML) Treatment Regimens

Clinical Trials: The National Comprehensive Network recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced healthcare team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are only provided to supplement the latest treatment strategies. These Guidelines are a work in progress that may be refined as often as new significant data becomes available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way. uInduction Therapy1

Note: All recommendations are Category 2A unless otherwise indicated. The NCCN believes the best option for any patient with cancer is in a and strongly encourages this option for all patients. PATIENT CRITERIA REGIMEN AND DOSING

Age <60 years2-8 Days 1–3: An anthracycline ( 60–90mg/m2 IV OR 12mg/m2) Days 1–7: 100–200mg/m2 continuous IV (Category 1). OR Days 1–3: Daunorubicin 60mg/m2 IV Days 1–7: Cytarabine 200mg/m2 continuous IV Days 1–5: 5 mg/m2. OR Days 1–3: An (daunorubicin 60mg/m2 IV OR idarubicin 12mg/m2 for 1 cycle) Days 1–6: High-dose cytarabine 2g/m2 IV every 12 hours OR Days 1–4: High-dose cytarabine 3g/m2 IV every 12 hours (Category 1 for patients ≤45 years, category 2B for other age groups). OR Days 1–3: Daunorubicin 60mg/m2 IV Days 1–7: Cytarabine 200mg/m2 continuous IV every 12 hours Days 8–21: 50mg orally every 12 hours.a OR Days 1, 3, 5: Dual-drug liposomal encapsulation of cytarabine 100mg/m2 + daunorubicin 44mg/m2 IV over 90 minutes (Category 2B).b OR Days 1, 4, 7: Daunorubicin 60mg/m2 + 3mg/m2 (up to one 4.5 mg vial) Days 1–7: Cytarabine 200mg/m2 continuous IV OR Days 1–7: SC -colony stimulating factor (G-CSF) Days 2–6: 30mg/m2 plus high-dose cytarabine 2g/m2 over 4 hours after starting fludarabine on days 2–6 Days 4–6: Idarubicin 8mg/m2 IV (Category 2B).

Age ≥60 years6-10 Days 1–3: An anthracycline (daunorubicin 60–90mg/m2 IV OR idarubicin 12mg/m2 IV OR 12mg/m2 IV) De novo AML without unfavorable Days 1–7: Cytarabine 100–200mg/m2 continuous IV. or molecular OR markers; no antecedent Days 1–3: Daunorubicin 60mg/m2 IV hematologic disorder; and no Days 1–7: Cytarabine 200mg/m2 continuous IV therapy-related AML Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1, 4, 7: Daunorubicin 60mg/m2 + gemtuzumab ozogamicin 3mg/m2 (up to one 4.5 mg vial) Days 1–7: Cytarabine 200mg/m2 continuous IV (for CD33-positive AML).

Age ≥60 years6,7,9,10 Lower-intensity therapy Unfavorable cytogenetics or Days 1–7: 5-azacytidine 75mg/m2 IV every 28 days molecular markers; antecedent OR hematologic disorder; therapy- Days 1–5: 20mg/m2 IV for a 4-week cycle. related AML OR Days 1–3: An anthracycline (daunorubicin 60–90mg/m2 IV OR idarubicin 12mg/m2 IV OR mitoxantrone 12mg/m2 IV) Days 1–7: Cytarabine 100–200mg/m2 continuous IV. OR Days 1–3: Daunorubicin 60mg/m2 IV Days 1–7: Cytarabine 200mg/m2 continuous IV Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1, 3, 5: Dual-drug liposomal encapsulation of cytarabine 100mg/m2 + daunorubicin 44mg/m2 IV over 90 minutes (Category 1).b -based regimens (Category 3).

continued

1 CancerTherapyAdvisor.com Acute (AML) Treatment Regimens

uInduction Therapy1 (continued)

PATIENT CRITERIA REGIMEN AND DOSING Age ≥60 years11-15 Lower-intensity therapy Not a candidate for intensive Days 1–10: Cytarabine 20mg SC twice daily. therapy or declines intensive OR therapy Days 1–7: 5-azacytidine 75mg/m2 IV every 28 days (preferred). OR Days 1–5: Decitabine 20mg/m2 IV every 28 days (preferred). OR Day 1: Gemtuzumab ozogamicin 6mg/m2 IV Day 8: Gemtuzumab ozogamicin 3mg/m2 IV (CD-33 positive). OR 100mg orally once daily (IDH-2 mutated AML). OR Best supportive care (hydroxyurea, transfusion support). uPost- Therapy1

Age <60 years12,13 Days 1, 3, and 5: High-dose cytarabine 3g/m2 IV over 3 hours every 12 hours for 3–4 cycles (Category 1) Core binding factor cytogenetic OR translocations without KIT Days 1–3: High-dose cytarabine 3g/m2 IV over 3 hours every 12 hours for 3–4 cycles. or favorable-risk OR molecular abnormalities Days 1–4: Cytarabine 1g/m2 every 12 hours Day 1: Gemtuzumab ozogamicin 3mg/m2 (up to 4.5mg vial) for 2 cycles Day 1 (Cycle 1) or Days 1–2 (Cycle 2): Daunorubicin 60mg/m2 IV (For CD33-positive AML).

Age <60 years Matched sibling or alternative donor HCT. Intermediate-risk and/or OR molecular abnormalities Days 1, 3, 5, OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours for 3–4 cycles. OR Days 1, 3, 5, OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1–4: Cytarabine 1g/m2 every 12 hours Day 1 (Cycle 1) or Days 1–2 (Cycle 2): Daunorubicin 60mg/m2 IV Day 1: Gemtuzumab ozogamicin 3mg/m2 (up to one 4.5mg vial) for 2 cycles (for CD33-positive AML).

Age <60 years Matched sibling or alternative donor HCT. Treatment-related disease other OR than CBF and/or poor-risk Days 1, 3, and 5 OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours for 3–4 cycles. cytogenetics and/or molecular OR abnormalities Days 1, 3, and 5 OR Days 1–3: High-dose cytarabine 1.5–3g/m2 IV over 3 hours every 12 hours. Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1 and 3: Dual-drug liposomal encapsulation of cytarabine 65mg/m2 + daunorubicin 29mg/m2 IV over 90 minutes (Category 2B).b

Age ≥60 years Reduced-intensity HCT. Complete Response After OR Previous Intensive Therapy Cytarabine 100–200mg/m2 IV for 5–7 days for 1–2 cycles ± anthracycline (idarubicin or daunorubicin). OR Cytarabine 1–1.5g/m2 IV for 4–6 doses for 1–2 cycles for patients with good performance status, normal renal function, better-risk or normal with favorable molecular markers. OR Days 1, 3, and 5: Cytarabine 1–1.5g/m2 over 3 hours every 12 hours Days 8–21: Midostaurin 50mg orally every 12 hours.a OR Days 1 and 3: Dual-drug liposomal encapsulation of cytarabine 65mg/m2 + daunorubicin 29mg/m2 IV over 90 minutes.b OR Days 1–4: Cytarabine 1000mg/m2 IV every 12 hours Day 1 (Cycle 1) OR Days 1–2 (Cycle 2): Daunorubicin 60mg/m2 IV Day 1: Gemtuzumab ozogamicin 3mg/m2 (up to one 4.5mg vial) for 2 cycles (for CD33-positive AML). OR Maintenance therapy with hypomethylating regimen (5-azacytidine, decitabine) every 4–6 weeks until progression. OR Observation.

continued

2 CancerTherapyAdvisor.com (AML) Treatment Regimens

uPost-Remission Therapy1 (continued)

PATIENT CRITERIA REGIMEN AND DOSING Age ≥60 years Allogeneic HCT (preferably in clinical trial). Induction Failure After Previous OR Intensive Therapy Best supportive care. Age ≥60 years Reduced-intensity HCT. Response After Previous Lower OR Intensity Therapy Continue hypomethylating regimens (5-azacytidine, decitabine) every 4–6 weeks until progression. OR Day 1: Gemtuzumab ozogamicin 2mg/m2 every 4 weeks up to 8 continuation courses (CD33-positive AML). OR Continue enasidenib until progression (IDH-2 mutated AML). Age ≥60 years Best supportive care. No Response or Progression After Previous Lower Intensity Therapy uTherapy for Relapse or Refractory Disease1

Age <60 years Chemotherapy* followed by matched sibling or alternative donor HCT. Early Relapse (<12 months) Age <60 years Chemotherapy* followed by matched sibling or alternative donor HCT. Late Relapse (≥12 months) OR Repeat initial successful induction regimen. Age ≥60 years Chemotherapy* followed by matched sibling or alternative donor HCT. Early Relapse (<12 months) OR Best supportive care. Age ≥60 years Repeat initial successful induction regimen. Late Relapse (≥12 months) OR Chemotherapy* followed by matched sibling or alternative donor HCT. OR Best supportive care. *Chemotherapy Aggressive therapy for appropriate patients: Options8-10, 14-19, 23, 24 Days 1–5: Cladribine 5mg/m2 IV Days 1–5: Cytarabine 2g/m2 IV Days 0–5: G-CSF 300mcg SC, ± Days 1–3: Mitoxantrone 10mg/m2 IV OR idarubicin 10mg/m2 IV. OR High-dose cytarabine (if not previously used in treatment) ± anthracycline. OR Days 1–5: Fludarabine 30mg/m2 IV over 0.5 hours Days 1–5: Cytarabine 2g/m2 IV over 4 hours Days 0 to polymorphonuclear recovery (>0.5 x 109/L): G-CSF 5mcg/kg or 300mcg/m2 (G-CSF may also start on Day +6 until engraftment) ± Days 1–3: Idarubicin 10mg/m2 IV. OR Days 1–6: 80mg/m2 IV over 1 hour + cytarabine 1g/m2 IV over 6 hours ± mitoxantrone 6mg/m2 IV bolus. OR Days 1–5: Clofarabine 22.5mg/m2–25mg/m2 IV ± Days 2–6: Cytarabine 0.75g/m2–2g/m 2 IV Days 0 to recovery: G-CSF 5mcg/kg/day ± Days 1–3: Idarubicin 6-8 mg/m2 IV. Less aggressive therapy: Hypomethylating agents (5-azacytidine or decitabine). OR Low-dose cytarabine (Category 2B). Therapy for patients with FLT3-ITD disease: Days 1–7: 5-azacytidine 75mg/m2 IV + sorafenib 400 mg orally twice daily continuously. OR Decitabine + sorafenib. Therapy for patients with IDH-2 disease Enasidenib 100mg orally daily. Therapy for CD33-positive disease Days 1, 4, 7: Gemtuzumuab ozogamicin 3mg/m2 IV over 2 hours.

continued

3 CancerTherapyAdvisor.com Acute Myeloid Leukemia (AML) Treatment Regimens

a This regimen is for FLT3 mutation-positive AML (both ITD and TKD) . While midostaurin was not FDA approved for maintenance therapy, the study was designed for consolidation and maintenance midostaurin for a total of 12 months. b For cytotoxic therapy-related AML other than core binding factor [CBF]/APL, or patients with antecedent MDS/CMML, or cytogenetic changes that are consistent with MDS

References

1. NCCN Clinical Practice Guidelines in ™. Acute ­Myeloid Leukemia. 16. Mayer RJ, Davis RB, Schiffer CA, et al. Intensive postremission chemotherapy in v1.2018. Available at: http://www.nccn.org/professionals/physician_gls/pdf/aml. adults with acute myeloid leukemia. Cancer and Leukemia Group B. N Engl J Med. pdf. Accessed March 29, 2018. 1994;331(14):896–903. 2. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute 17. Jaramillo S, Benner A, Krauter J, et al. Condensed versus standard schedule of myeloid leukemia. N Engl J Med. 2009;361(13): 1249–1259. high-dose cytarabine consolidation therapy with pegfilgrastim growth factor 3. Kern W, Estey EH. High-dose arabinoside in the treatment of acute support in acute myeloid leukemia. Cancer J. 2017;7:e564, myeloid leukemia review of three randomized trials. Cancer. 2006;107(1): 18. Löwenberg B, Pabst T, Vellenga E, et al; Dutch-Belgian Cooperative Trial Group for 116–124. Hemato-Oncology (HOVON) and Swiss Group for Clinical Cancer Research (SAKK) 4. Weick JK, Kopecky KJ, Appelbaum FR, et al. A randomized investigation of high- Collaborative Group. Cytarabine dose for acute myeloid leukemia. N Engl J Med. dose versus standard-dose cytosine arabinoside with daunorubicin in patients 2011;364(11):1027–1036. with previously untreated acute myeloid leukemia: a Southwest Oncology Group 19. Wierzbowska A, Robak T, Pluta A, et al; Polish Adult Leukemia Group. Cladribine study. Blood. 1996:88(8):2841–2851. combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF 5. Bishop JF, Matthews JP, Young GA, et al. A randomized study of high-dose (CLAG-M) is a highly effective salvage regimen in patients with refractory and cytarabine in induction in acute myeloid leukemia. Blood. 1996;87(5):1710–1717. relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol. 2008;80(2):115-126. 6. Lancet JE, Uy GL, Cortes JE, et al. Final results of a phase III randomized trial of CPX-351 versus 7+3 in older patients with newly diagnosed high risk (secondary) 20. Fridle C, Medinger M, Wilk MC, et al. Cladribine, cytarabine and idarubicin (CLA-Ida) AML. J Clin Oncol. 2016;34(suppl):abstract 7000. salvage chemotherapy in relapsed acute myeloid leukemia (AML). Leuk . 2017;58(5):1068–1075. 7. Castaigne S, Pautas C, Terre C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): 21. Martin MG, Welch JS, Augustin K, et al. Cladribine in the treatment­ of acute a randomised, open label, phase 3 study. Lancet. 2012;379:1508-1516. myeloid leukemia: a single-institution ­experience. Clin Lymphoma Myeloma. 2009;9(4):298–301. 8. Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: 22. Montillo M, Mirto S, Petti MC, et al. Fludarabine, cytarabine, and G-CSF (FLAG) results of the MRC AML15 trial. J Clin Oncol. 2011;29:369-377. for the treatment of poor risk acute myeloid­ leukemia. Am J Hematol. 1998;58(2): 105–109. 9. Krug U, Röllig C, Koschmieder A, et al. Complete remission and early after intensive chemotherapy in patients aged 60 years or older with acute myeloid 23. Parker JE, Pagliuca A, Mijovic A, et al. Fludarabine, cytarabine, G-CSF and idarubicin leukaemia: a web-based application for prediction of outcomes. Lancet. 2010; (FLAG-IDA) for the treatment of poor-risk myelodysplastic syndromes and acute 376(9757):2000–2008. myeloid leukaemia. Br J Haematol. 1997;99(4):939–944. 10. Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin 24. Amadori S, Arcese W, Isacchi G, et al. Mitoxantrone, etoposide, and intermediate- in older patients with acute myeloid leukemia.­ N Engl J Med. 2009;361(13): dose cytarabine: an effective and tolerable regimen for the treatment of refractory 1235–1248. acute myeloid leukemia. J Clin Oncol. 1991;9(7):1210–1214. 11. Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and 25. Becker PS, Kantarjian HM, Appelbaum FR, et al. Clofarabine with high dose hydroxyurea with or without all-trans retinoic­ acid for acute myeloid leukemia cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapse and high-risk in patients not considered fit for intensive and refractory acute myeloid leukaemia. Br J Haematol. 2011;155(2):182–189. treatment. Cancer. 2007;109(6):1114–1124. 26. Faderl S, Ferrajoli A, Wierda W, et al. Clofarabine combinations as acute myeloid 12. Fenaux P, Mufti GJ, Hellstrom-Lindberg E, et al. Efficacy of compared leukemia salvage therapy. Cancer. 2008; 113(8):2090–2096. with that of conventional care regimens in the treatment of higher-risk 27. Ravandi F, Alattar ML, Grunwald MR, et al. Phase 2 study of azacytidine plus myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet sorafenib in patients with acute myeloid leukemia and FLT-3 internal tandem Oncol. 2009;10(3):223–232. duplication mutation. Blood. 2013:121(23):4655–4662. 13. Cashen AF, Schiller GJ, O’Donnell MR, DiPersio JF. Multicenter, phase II study 28. Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or of decitabine for the first-line treatment of older patients with acute myeloid refractory acute myeloid leukemia. Blood. 2017;130:722–731. leukemia. J Clin Oncol. 2010;28(4):556–561 29. Taksin AL, Legrand O, Raffoux E, et al. High efficacy and safety profile of 14. Kantarjian HM, Erba HP, Claxton D, et al. Phase II study of clofarabine­ monotherapy fractionated doses of Mylotarg as induction therapy in patients with relapsed in previously untreated older adults with acute myeloid leukemia and unfavorable acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia. prognostic factors.­ J Clin Oncol. 2010;28(4):549–555. 2007;21: 66–71. 15. Stein EM, DiNardo CD, Altman JK, et al. Safety and efficacy of AG-221, a potent in- hibitor of mutant IDH2 that promotes differentiation of myeloid cells in patients with advanced hematologic : results of a phase 1/2 trial. Blood. 2015. 2015:126(23):323

(Revised 3/2018) © 2018 by Haymarket Media, Inc.

4 CancerTherapyAdvisor.com